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Biomedical subjects

H M Jansen

Publications and source records attributed to H M Jansen.

At least 73 records · Page 4Linked to original sources
PubMed1997

Differences in nonspecific bronchial responsiveness between patients with asthma and patients with rhinitis are not explained by type and degree of inhalant allergy.

Patients with allergic asthma have higher levels of nonspecific bronchial responsiveness than patients with allergic rhinitis. The aim of the study was to investigate whether this is caused by differences in the degree of allergy to inhalant allergens between asthmatics and rhinitics. Therefore, bronchial responsiveness to histamine was measured in 25 allergic patients with isolated upper airways symptoms. Nonspecific bronchial responsiveness in this group was compared with nonspecific bronchial responsiveness in a group of 136 patients with allergic asthma, with allergy and % predicted FEV1 as confounding variables. In addition, a matched pair analysis was performed. Twenty-five patients with nonallergic rhinitis served as controls to evaluate the influence of an IgE-independent inflammatory reaction in the upper respiratory tract on the level of bronchial responsiveness. Furthermore, we investigated the level of nonspecific responsiveness in 18 healthy controls. In the patients with allergic asthma, a correlation was found between nonspecific bronchial responsiveness and IgE against indoor allergens (n = 136, r = 0.34, p < 0.001) and % predicted FEV1 (n = 136, r = 0.37), p < 0.001). Patients with allergic asthma and patients with allergic rhinitis differed with respect to the level of bronchial responsiveness (p < 0.001), and the amount of specific IgE antibodies against indoor allergens (p = 0.01). The difference in level of bronchial responsiveness remained (p < 0.001) after correction with % predicted FEV1 and specific IgE against indoor allergens as confounding variables. Similarly, after matching of patients with allergic rhinitis (n = 25) with patients with allergic asthma (n = 25) regarding the specific IgE, total IgE and age of the patients, the difference in level of bronchial responsiveness remained (p < 0.001). Patients with nonallergic rhinitis had higher levels of nonspecific bronchial responsiveness than healthy controls and did not differ from patients with allergic rhinitis. In conclusion, the results confirm that IgE against common indoor allergens plays an important role in the mechanism underlying nonspecific bronchial hyperresponsiveness. However, differences in bronchial responsiveness between patients with asthma and patients with rhinitis are not merely explained by differences in the IgE antibody concentrations.

Adolescent↗
PubMed1997

Nedocromil sodium in obstructive airways disease: effect on symptoms and plasma protein leakage in sputum.

In patients with asthma or chronic obstructive pulmonary disease, there is chronic airway inflammation with increased leakage of plasma proteins into the airway lumen, which can be reduced by inhaled glucocorticosteroids. Nedocromil sodium is an anti-inflammatory drug, and we questioned whether it also affects the leakage of plasma proteins. In a double-blind placebo-controlled study we investigated the effect of 12 weeks of treatment with nedocromil on forced expiratory volume in one second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20), peak flow, symptom scores, and plasma protein leakage in sputum, in 31 patients with obstructive airways disease and sputum production (mean (range) FEV1 61% of predicted (42-87%); geometric mean (range) PC20 0.39 (0.04-2.9) mg x mL(-1)). As a measure for plasma protein leakage we calculated the relative coefficients of excretion (RCE) of proteins from serum to the soluble phase of sputum. There was a small increase in morning and evening peak flow (p<0.05) and a decrease in night-time bronchodilator use (p<0.02) in favour of nedocromil. The RCE of alpha2-macroglobulin to albumin significantly decreased after treatment with nedocromil (p=0.03). The results show limited clinical efficacy of nedocromil in our study group. They further suggest that the anti-inflammatory properties of nedocromil extend to inhibition of plasma protein leakage into the airways.

Anti-Inflammatory Agents↗
PubMed1997

Persisting Haemophilus influenzae strains induce lower levels of interleukin-6 and interleukin-8 in H292 lung epithelial cells than nonpersisting strains.

Nonencapsulated Haemophilus influenzae strains isolated from patients with chronic bronchitis can be divided into those that persist in the lower respiratory tract and those that do not. We tested the hypothesis that persisting and nonpersisting strains differ in the extent to which they activate epithelial cells to produce two potent inflammatory mediators, interleukin (IL)-6 and IL-8. A suspension of 10(7) and 10(8) colony forming units (cfu) x mL(-1) of H. influenzae, persisting and nonpersisting, induced a dose- and time-dependent production of IL-6 and IL-8 by the human pulmonary mucoepidermoid carcinoma-derived cell line H292, but levels of IL-6 were lower after exposure to persisting H. influenzae (p<0.05). IL-8 production showed a similar trend (p<0.02; analysis of variance). H. influenzae bacteria that adhered to H292 cells were equally distributed over persisting and nonpersisting isolates and induced IL-6 and IL-8 levels similar to their nonadhering counterparts. The difference between persisting and nonpersisting H. influenzae was not due to cytotoxic, antimetabolic or antiproliferative effects on H292 cells. Furthermore, pre-exposure of cells to persisting and nonpersisting isolates did not block subsequent IL-1beta-induced IL-6 production. We conclude that persisting clinical isolates induce less interleukin-6 and interleukin-8 in H292 cells than nonpersisting isolates, probably because they excrete lower amounts of a stimulus of H292 cells. The stimulus is heat stable, hydrophilic and nonproteinous and probably not lipopolysaccharide alone. These findings support the suggestion that some strains of Haemophilus influenzae that persist in the airways of patients, may do so because they induce only a weak inflammatory response.

Analysis of Variance↗
PubMed1997

55Co-PET in stroke: relation to bloodflow, oxygen metabolism and gadolinium-MRI.

BACKGROUND: Several studies have shown the feasibility of Co-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerosis, cerebral tumors and trauma. These studies indicate that Co-isotopes allow visualization of brain pathology related to inflammatory processes, reactive gliosis and cell death. Until now, it is not clear if 55Co accumulation occurs in the core of infarction or in the penumbra. Therefore, in the present study, we compared 55Co-PET with functional parameters such as cerebral bloodflow (rCBF) using C15O2, oxygen metabolism (rCMRO2) using 15O2 and cerebral bloodvolume (CBV) using C15O in PET and with the anatomical parameter Gd-MRI. PATIENTS AND METHODS: Seventeen patients (11 male; 6 female) age 43 to 84 (mean 69) with middle cerebral artery (mca) stroke, as proven by CT or MRI, were examined with 55Co-PET (0.5-1.0 mCi 55CoCl2), C15O2-, 15O2- and C15O-PET in one session 0-30 days after stroke-onset. Regions of infarction were defined by rCMRO2 being smaller than 65% or rCBF below 45% of the contralateral value and were subsequently superimposed on the cobalt scan. To compare the Cobalt uptake with the Gd-MRI, a realignment program was used that matches the MRI with the bloodflow images. Clinical status was established using the Orgogozo stroke scale at admission and at discharge (at least 6 weeks after admission) and the Barthel index. RESULTS: Eight patients showed a positive Co-PET scan and were used for further analysis. It appeared that Co accumulates in areas with a diminished oxygen metabolism and with a preserved bloodflow. We found Co-uptake in only a part of the Gd enhanced brain tissue with a tendency to be located peripherally or outside the Gd demarcated brain tissue. CONCLUSION: The results of the present study suggest that Co accumulates into infarcted brain tissue with a rather preserved flow independently of blood-brain barrier breakdown.

Adult↗
PubMed1997

Co-registration of PET and MRI in different courses of MS using Cobalt-55 as a Calcium-tracer.

Multiple Sclerosis (MS) is an auto-immune central nervous system (CNS) inflammation. At this moment, MRI is the most accurate paraclinical test in MS to monitor disease activity, although poorly correlated with clinical impairment. PET using Co-55 as a Ca-tracer may visualize Co-transport across the neuronal membrane, Ca-mediated inflammatory processes and passive leakage through a breach in the blood-brain barrier. Co-registration of MRI and Co-PET may actually allow identification of clinically active lesions. MRI and Co-PET were performed as described elsewhere. Based on a statistic parametric mapping (SPM-96)-software package, MRI and Co-PET were superimposed. A semi-automated technique was used to count the MS-lesions. We included four groups of eight MS-patients with relapsing-remitting (RR), primary progressive (PP), progressive relapsing (PR) and secondary progressive (SP) courses and eight healthy volunteers. MS was assessed in terms of impairment using Kurtzke's Expanded Disability Status Scale (EDSS) and Scripps Neurological Rating Scale (NRS). Co-PET displayed focal uptake throughout the MS brain, both in the grey and white matter. All four patients groups (as compared to controls) demonstrated a more inhomogeneous distribution of Co-spots with a tendency to show clustering, most evident in RR-MS. SPM-analysis revealed an essentially different distribution pattern of MS spots on MRI and Co-PET. (Merging of) Co-PET and MRI may eventually form complementary tools for identifying clinically relevant lesions, thus providing a more reliable secondary outcome measure in MS.

Brain↗
PubMed1996

The relationship between RAST and skin test results in patients with asthma or rhinitis: a quantitative study with purified major allergens.

BACKGROUND: Study of the relationship between skin test results and IgE antibody levels is seriously hampered by the use of conventional allergen extracts because the precise amount of relevant allergen for each patient is unknown. OBJECTIVE: This study was designed to investigate skin reactivity with purified major allergens and to assess the relation with serum levels of IgE antibodies and to determine which additional factors contribute to the skin test result. METHODS: We used five purified major allergens (Der p 1, Der p 2, Fel d 1, Lol p 1, and Lol p 5) in skin tests, RASTs, and histamine release tests in 43 multisensitized patients with asthma or rhinitis. RESULTS: The differences in biologic activity of the five major allergens at a given level of specific IgE are within one order of magnitude. A significant residual variation remains in the correlation between skin test results and levels of IgE antibodies, which cannot be explained by imprecision of both tests (Pearson log skin test vs log specific IgE: r = 0.46-0.92). With similar levels of specific IgE, the amount of allergen that is required for a positive skin test result may differ by as much as a factor of 100 between patients. The amount of total IgE in serum contributes significantly to the skin test result. High values of total IgE are accompanied by a lower skin reactivity for allergen. Within individuals, allergens that cause skin test results that deviate from the prediction based on IgE antibody level often show a similar deviation in the histamine release test. This indicates that the type of IgE response (i.e., affinity or epitope recognition pattern) contributes significantly to the skin test result. Skin reactivity for histamine does not significantly influence the skin reactions expressed as allergen threshold. However, increased skin reactions with higher allergen dosages depend on histamine reactivity. CONCLUSION: The major allergens tested show similar biologic activities. In addition to IgE antibody level, total serum IgE and type of IgE antibody response contribute significantly to the skin test threshold for allergens. Even in a system with purified allergens, IgE antibody levels and skin test results are not interchangeable as an indicator of the degree of allergic sensitization.

Adolescent↗
PubMed1996

Histamine-releasing activity in supernatants of mononuclear cells: contribution of monocyte chemotactic protein-1 activity compared with IgE-dependent activity.

BACKGROUND: Supernatants of cultured human mononuclear cells contain factors that induce histamine release from basophils. Some of the histamine-releasing factors present are IgE-independent, but an IgE-dependent form has also been described. The IgE that does respond to the IgE-dependent histamine-releasing factor was defined as IgE+. OBJECTIVE: This study was conducted to analyze the contribution of chemokines, such as monocyte chemotactic protein-1 (IgE-independent), to improve the detection of IgE-dependent histamine-releasing factor. METHODS: Supernatants were prepared from mononuclear cells of three subjects. Monocyte chemotactic protein-1 content and histamine-releasing activity (HRA) were measured. Depletion of chemokine activity was carried out with heparin-Sepharose (Pharmacia, Uppasala, Sweden). RESULTS: Replacing IgE- on basophils with IgE+ serum decreased the correlation between monocyte chemotactic protein-1 and histamine release (rho = 0.80, n = 280 vs p = 0.12, n = 18; p for difference between p values; < 0.05). After depletion of chemokines in three supernatants derived from mononuclear cells, IgE-dependent HRA was still present. CONCLUSION: We conclude that in supernatants derived from mononuclear cells, the IgE-independent HRA masks the IgE-dependent HRA. The latter can be more clearly detected after depletion of chemokine activity with heparin-Sepharose.

Animals↗
PubMed1996

False-positive skin prick test responses to commercially available dog dander extracts caused by contamination with house dust mite (Dermatophagoides pteronyssinus) allergens.

BACKGROUND: In an outpatient population, a high frequency of positive skin prick test responses to dog dander was found in the absence of detectable IgE to dog dander in the RAST. The majority of these patients were sensitized to house dust mites (Dermatophagoides pteronyssinus) and had no obvious dog-related allergic symptoms. These findings prompted us to investigate whether dog dander skin test preparations are contaminated with house dust mite allergens in amounts sufficient to cause false-positive skin prick test responses in patients sensitized to house dust mites. METHODS: Antigen detection assays with monoclonal and polyclonal antibodies were used to determine concentrations of the major allergen Can f 1 from dog dander and the major allergens Der p 1 and Der p 2 from house dust mites in five commercially available dog dander skin prick test preparations (A to E). RESULTS: Can f 1 concentrations varied for the different extracts (A: 170 micrograms/ml, B: 11.1 micrograms/ml, C: 13.3 micrograms/ml, D: 3.8 micrograms/ml, and E: 59.4 micrograms/ml). Der p 1 was detectable in all extracts (A: 33.4 ng/ml, B:5.1 ng/ml, C:29.6 ng/ml, D: 0.4 ng/ml, and E: 1.9 ng/ml), and Der p 2 was detectable in some of the commercially available dog dander skin prick test preparations tested (A: 31.3 ng/ml, B: 3.0 ng/ml, and C: 7.5 ng/ml). The median house dust mite threshold in the skin prick test was found to be 5.8 ng/ml, of Der p 1 (range, 3.5 to 20.8 ng/ml) in nine patients tested. CONCLUSION: Contamination of commercially available dog dander skin prick test preparations with the major allergens (Der p 1 and Der p 2) of the house dust mite (D. pteronyssinus) was demonstrated. These contaminations cause false-positive responses to skin prick tests with dog dander in patients sensitized to house dust mite.

Allergens↗
PubMed1996

Effect of local allergen priming on early, late, delayed-phase, and epicutaneous skin reactions.

Allergic disease is reflected in a chronic inflammatory response to an allergen. It is thought that local allergen priming underlies this chronicity. To assess the effect of allergen priming on the amplitude and histologic effect of the allergic reaction, four sequential, intracutaneous skin tests were done with 48-h intervals in 13 patients allergic to the house-dust mite Dermatophagoides pteronyssinus (Dpt). Reactions were measured at 15 min, and at 6, 24, and 48 h. Subsequently, epicutaneous tests were done on Dpt-primed spots (n = 5). At 6, 24, and 48 h, reactions increased after priming (P < 0.006), with unaltered early reactions. Epicutaneous reactions to Dpt on primed spots were larger than in epicutaneous controls on similarly primed skin. Local intradermal priming results in greater inflammatory responses at both intra- and epicutaneous challenge. This mechanism may explain the chronicity of allergic reactions at epithelial surfaces.

Allergens↗
PubMed1996

Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness.

In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC20 histamine after 24 h. When the group was divided into three subgroups according to baseline PC20 histamine, a significant decrease in PC20 histamine was found only in patients with relatively high baseline PC20 histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC20 and allergen-induced PC20 histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC20 histamine; no further decrease in mean PC20 histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC20 values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.

Adolescent↗
PubMed1996

Fine mapping of outer membrane protein P2 antigenic sites which vary during persistent infection by Haemophilus influenzae.

Antigenic drift of the major outer membrane protein (MOMP) P2 of nonencapsulated Haemophilus influenzae as observed during persistent infections in patients with chronic bronchitis was mimicked in a rabbit model in which H. influenzae persisted in subcutaneous cages. The antigenic drift resulted from amino acid substitutions in potentially surface-exposed loops of MOMP P2. Since in a rabbit model the appearance of antigenic variants was associated with the presence of strain-specific bactericidal antibodies (L. Vogel, B. Duim, F. Geluk, P. Eijk, H. Jansen, J. Dankert, and L. van Alphen, Infect. Immun. 64:980-986, 1996), we determined the epitope specificities of these bactericidal antibodies. The eight loops of MOMP P2 of H. influenzae d1 were separately expressed as fusion proteins with glutathione S-transferase. Sera of rabbits persistently infected with H. influenzae reacted with the loop 5 and loop 6 fusion proteins in immunoblotting and enzyme-linked immunosorbent assay. For fine mapping of the epitopes with pepscan analysis, overlapping synthetic peptides consisting of 12 amino acids were made. Rabbit sera contained antibodies reacting with peptides derived from loop 5 and peptides containing amino acids of the side of loop 6. In addition, MOMP P2 variant-specific reactions with the amino acids located at the tip of loop 6 were detected. The rabbit sera showed variant-specific complement-dependent bactericidal activities, which were eliminated by affinity chromatography with fusion proteins of loop 6 but not of loop 5. We conclude that, during persistence of H. influenzae in rabbits, variant-specific bactericidal antibodies are elicited to the variable tip of MOMP P2 loop 6.

Animals↗
PubMed1996

Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study.

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury.

Brain Injuries↗
PubMed1996

Interleukin-8 in airway inflammation in patients with asthma and chronic obstructive pulmonary disease.

We have investigated whether IL-8 is present in airway secretions from patients with asthma and chronic obstructive pulmonary disease (COPD) to obtain information on its possible role in airway inflammation in obstructive airways disease. In the bronchoalveolar lavage fluid (BALF) from 11 clinically stable patients with asthma the levels of IL-8 were increased compared to 10 healthy subjects (median: controls 21.5 pg/ml, asthma 244 pg/ml: p < 0.005). In the patients with asthma the levels of IL-8 correlated with the percentage neutrophils in the BALF (r = 0.81; p < 0.001) and with a parameter of the permeability of the respiratory membrane, the quotient (alpha 2-macroglobulin in BALF)/(alpha 2-macroglobulin in serum) (r = 0.66; p < 0.025). In the sputum sol phase of 9 patients with symptomatic asthma the levels of IL-8 were lower than in 9 patients with COPD (asthma: 6.4 ng/ml; COPD: 16.3 ng/ml; p < 0.02) and significantly correlated with those of neutrophilic myeloperoxidase (MPO; r = 0.85; p < 0.005). The increased levels of IL-8 in the airway secretions from both patients with asthma and COPD may be markers of an ongoing inflammatory process, which is more pronounced in patients with COPD. In patients with asthma the strong correlation between the levels of IL-8 and the percentage neutrophils and/or the levels of MPO points to a role of IL-8 in the recruitment and activation of neutrophils in the airway lumen.

Adolescent↗
PubMed1996

Fel d 1-specific IgG antibodies induced by natural exposure have blocking activity in skin tests.

Cat-allergic patients frequently have IgG antibodies directed against Fel d 1. The aim of this study was to investigate whether these IgG antibodies influence the results of the skin test. Titrated skin tests were performed with Fel d 1 and IgE and IgG antibody levels were measured in 59 patients with cat allergy. Levels of specific IgG against Fel d 1 ranged from less than 0.25 to 3.5 microgram/ml. By means of a multiple regression analysis it was shown that the amount of specific IgG antibodies contributes significantly to the results of the skin test. Presence of specific IgG against Fel d 1 was accompanied by higher skin thresholds for Fel d 1. In conclusion, this study indicates that even low levels of specific IgG, induced by natural exposure to cat allergens, have a blocking effect on the early phase skin reaction.

Adolescent↗
PubMed1996

Production and modulation of T-cell cytokines in atopic allergy.

Atopic allergy is associated with allergen-specific CD4+ T cells showing a bias to production of the type-2 cytokines interleukin (IL)-4 and IL-5. There are indications that this bias is also evident in atopic T-helper (Th) cells with other antigen specificities. The balance between the production of type-1 and type-2 cytokines is influenced by various factors present in the microenvironment of the Th cells during their activation. Factors of special interest are antigen-presenting cell-derived IL-12 and prostaglandin E2, skewing to type-1 and type-2 cytokine production, respectively. The production of IL-12 and prostaglandin E2 is induced by the interaction between CD40 and CD40 ligand expressed by Th cells, and by biologically active agents such as micro-organisms or their products. The IL-12/prostaglandin E2 production ratio depends on the antigen-presenting cell type, the type of stimulus and the presence of certain cytokines. Other Th-cytokine-skewing factors are autocrine or paracrine IFN-gamma and IL-4. In fact, the type-1/type-2 cytokine production balance in Th cells is under the control of various soluble products that act in a complex network of type-1 (e.g. IL-12, IFN-gamma) or type-2 (e.g. IL-4, IL-10 and prostaglandin E2) factors and are produced by Th cells and their accessory antigen-presenting or bystander cells. The levels of these factors may further be determined by gene polymorphisms or aberrant hormone levels. Despite the growing knowledge of the regulation of Th-cell cytokine production, the etiology of biased cytokine production in atopic allergic individuals is still enigmatic.

Animals↗
PubMed1996

Reactivity to IgE-dependent histamine-releasing activity in asthma or rhinitis.

We investigated the relation between IgE reactive with histamine-releasing factor (HRF) and clinical status in patients with asthma or rhinitis. Sera were used to passively sensitize purified, lactic-acid treated basophils. IgE-independent HRF due to chemokines was removed from mononuclear cell supernatants with heparin-Sepharose. IgE-dependent HRF was determined by measuring the increase in histamine release between 1 min and 60 min, which was designated delta HRF. HRF-reactive IgE was demonstrable in nine of 18 patients with allergic asthma, three of 19 patients with nonallergic asthma, five of 17 patients with allergic rhinitis, and none of 19 control patients. The presence of HRF-reactive IgE was associated with: (1) IgE to inhalant allergens; 40% of radioallergosorbent test (RAST)-positive individuals versus 8% of RAST-negative individuals were positive (OR = 7.8, p < 0.005); (2) bronchial sensitivity to histamine in all asthmatic patients (geometric mean PC20: 1.50 versus 0.51 mg/ml; p < 0.005); and (3) bronchial sensitivity to histamine in allergic asthmatic patients (geometric mean PC20: 1.27 versus 0.37 mg/ml, p < 0.02). These findings support the hypothesis that IgE-dependent HRF might contribute to the chronic allergic reaction.

Adolescent↗
PubMed1996

Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms.

Glucocorticosteroids (GCS) are beneficial in allergic asthma. GCS therapy results in reduced mRNA expression of interleukin-4 (IL-4) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. In vitro studies with blood-derived T cells, however, show inhibition of all three cytokines by GCS. We studied the effects of GCS on T cells from BAL in vitro, namely Th0-, Th1, and Th2-like clones; and we compared BAL- with blood-derived clones. Dexamethasone (DEX) inhibited the anti-CD3-induced production of IL-4, IL-5 and IFN-gamma in all 20 clones tested. IFN-gamma production was inhibited significantly less than IL-4 and IL-5. DEX enhanced the ratio IFN-gamma/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers DEX inhibited IL-2 production partially and enhanced IL-2R alpha expression and proliferation. Anti-IL-2 and anti-IL2R alpha blocked the DEX-induced increase in proliferation. High levels of added IL-2 induced the second type of response. In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by DEX than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. The differential effects of DEX on the proliferation of high and low IL-2 producers in vitro may implicate a selective outgrowth of Th1-like T cells in vivo in patients treated with steroids.

Antibodies↗